pH-Sensitive Polymeric Vesicles for GOx/BSO Delivery and Synergetic Starvation-Ferroptosis Therapy of Tumor

Typical glucose oxidase (GOx)-based starvation therapy is a promising strategy for tumor treatment; however, it is still difficult to achieve an effective therapeutic effect via a single starvation therapy. Herein, we designed a pH-sensitive polymeric vesicle (PV) self-assembled by histamine-modified chondroitin sulfate (CS-his) for codelivery of GOx and L-buthionine sulfoximine (BSO). GOx can consume glucose to induce the starvation therapy after the PVs reach cancer cell. Moreover, the product H2O2 will be reduced by a high concentration of glutathione (GSH) in the tumor cell, resulting in a reduction of the GSH content. The released BSO finally further reduced the GSH level. As a result, the signaling pathway of the ferroptosis will be activated. The in vivo results demonstrated that GOx/BSO@CS PVs exhibit a good inhibitory effect on the growth of 4T1 tumors in mice. Thus, this work provides a facile strategy to prepare pH-sensitive nanomedicine for synergistic starvation-ferroptosis therapy of tumor.

Automated summary

This study developed a pH-sensitive polymeric vesicle for co-delivery of GOx and BSO, which can induce starvation therapy in cancer cells by consuming glucose and activating the ferroptosis signaling pathway. In vivo results showed that GOx/BSO@CS PVs effectively inhibited the growth of 4T1 tumors in mice, indicating a promising strategy for synergistic starvation-ferroptosis therapy in tumor treatment.